Metformin, a widely prescribed medication for type 2 diabetes, has been shown to slow the growth of precancerous cells in the esophagus, according to a recent study published in Nature Genetics. The research, conducted by scientists at the Wellcome Sanger Institute, suggests that the drug may have a role beyond diabetes management in preventing squamous esophageal cancer.
The study, which combined experiments in mice, cell cultures, and DNA sequencing of human samples, focused on mutations in the PIK3CA gene, known to drive aggressive cell growth. The team found that cells with PIK3CA mutations grow faster than normal cells, and that this growth is enhanced by metabolic conditions such as a high-fat diet and type 1 diabetes in mice. Analysis of human esophagus samples revealed that overweight individuals had a higher prevalence of cells with PIK3CA mutations, suggesting a link between obesity and esophageal cancer risk.
Metformin's Impact on Mutant Cells
Interestingly, the researchers discovered that metformin treatment reversed the growth advantage of these mutant cells. Both in mice and in lab-grown cells, metformin caused the PIK3CA-mutated cells to lose their proliferative edge. This effect was observed even in non-diabetic mice, suggesting a mechanism independent of metformin's blood sugar-lowering effects.
Clinical Implications and Future Research
Esophageal cancer is a significant health concern, with approximately 9,200 new cases diagnosed annually in the U.K. and a poor five-year survival rate of around 17%. These cancers often arise from mutated cells in the esophagus, highlighting the importance of understanding the factors that promote their growth.
"As we age, our bodies accumulate mutated cells. Learning what factors cause cells carrying these cancer-related mutations to grow long before cancer develops opens the door to new prevention strategies," said Dr. Albert Herms, one of the study's lead researchers.
Dr. Phil Jones added, "Our findings show how a common, safe medication like metformin might be used in new ways to prevent cancers related to PIK3CA mutations. This discovery could offer a new tool for cancer prevention, especially in people at higher risk due to metabolic disorders."
While previous epidemiological studies have hinted at a potential link between metformin and reduced cancer incidence in diabetic populations, the specific mechanisms of action and the populations that may benefit have remained unclear. This new research provides insights into how metformin may impact the growth of cells carrying PIK3CA mutations, opening the door to repurposing the drug for cancer prevention.
Next Steps
Further clinical trials are needed to determine the optimal administration of metformin for cancer prevention and to identify the patients who would benefit most from this approach. The researchers emphasize that this study represents an important first step in exploring the potential of metformin to prevent esophageal cancer.
"One of the quickest ways to improve cancer outcomes is finding new purposes for existing drugs. This research gives us an important first glimpse into ways in which metformin could be used to prevent oesophageal cancer, though further clinical trials are needed to understand how it should be administered, and which patients could benefit most," says Dr. Iain Foulkes.
